Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501Y<sub>MA30</sub> Strain of SARS-CoV-2
The Omicron SARS-CoV-2 variant has been designated as a variant of concern because its spike protein is heavily mutated. In particular, the Omicron spike is mutated at five positions (K417, N440, E484, Q493, and N501) that have been associated with escape from neutralizing antibodies induced by eith...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/8/1172 |
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| author | Karen V. Kibler Mateusz Szczerba Douglas Lake Alexa J. Roeder Masmudur Rahman Brenda G. Hogue Lok-Yin Roy Wong Stanley Perlman Yize Li Bertram L. Jacobs |
| author_facet | Karen V. Kibler Mateusz Szczerba Douglas Lake Alexa J. Roeder Masmudur Rahman Brenda G. Hogue Lok-Yin Roy Wong Stanley Perlman Yize Li Bertram L. Jacobs |
| author_sort | Karen V. Kibler |
| collection | DOAJ |
| description | The Omicron SARS-CoV-2 variant has been designated as a variant of concern because its spike protein is heavily mutated. In particular, the Omicron spike is mutated at five positions (K417, N440, E484, Q493, and N501) that have been associated with escape from neutralizing antibodies induced by either infection with or immunization against the early Washington strain of SARS-CoV-2. The mouse-adapted strain of SARS-CoV-2, SARS2-N501Y<sub>MA30</sub>, contains a spike that is also heavily mutated, with mutations at four of the five positions in the Omicron spike associated with neutralizing antibody escape (K417, E484, Q493, and N501). In this manuscript, we show that intranasal immunization with a pre-fusion stabilized Washington strain spike, expressed from a highly attenuated, replication-competent vaccinia virus construct, NYVAC-KC, fully protected mice against symptoms and death from SARS2-N501Y<sub>MA30</sub>. Similarly, immunization by scarification on the skin fully protected against death, but not from mild disease. This data demonstrates that the Washington strain spike, when expressed from a highly attenuated, replication-competent poxvirus—administered without parenteral injection—can fully protect against the heavily mutated mouse-adapted SARS2-N501Y<sub>MA30</sub>. |
| first_indexed | 2024-03-09T09:48:01Z |
| format | Article |
| id | doaj.art-9b8ece6e86844cca8f4922d870287460 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T09:48:01Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-9b8ece6e86844cca8f4922d8702874602023-12-02T00:24:41ZengMDPI AGVaccines2076-393X2022-07-01108117210.3390/vaccines10081172Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501Y<sub>MA30</sub> Strain of SARS-CoV-2Karen V. Kibler0Mateusz Szczerba1Douglas Lake2Alexa J. Roeder3Masmudur Rahman4Brenda G. Hogue5Lok-Yin Roy Wong6Stanley Perlman7Yize Li8Bertram L. Jacobs9Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ 85287, USABiodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ 85287, USASchool of Life Sciences, Arizona State University, Tempe, AZ 85287, USASchool of Life Sciences, Arizona State University, Tempe, AZ 85287, USABiodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ 85287, USABiodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ 85287, USADepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USADepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USABiodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ 85287, USABiodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ 85287, USAThe Omicron SARS-CoV-2 variant has been designated as a variant of concern because its spike protein is heavily mutated. In particular, the Omicron spike is mutated at five positions (K417, N440, E484, Q493, and N501) that have been associated with escape from neutralizing antibodies induced by either infection with or immunization against the early Washington strain of SARS-CoV-2. The mouse-adapted strain of SARS-CoV-2, SARS2-N501Y<sub>MA30</sub>, contains a spike that is also heavily mutated, with mutations at four of the five positions in the Omicron spike associated with neutralizing antibody escape (K417, E484, Q493, and N501). In this manuscript, we show that intranasal immunization with a pre-fusion stabilized Washington strain spike, expressed from a highly attenuated, replication-competent vaccinia virus construct, NYVAC-KC, fully protected mice against symptoms and death from SARS2-N501Y<sub>MA30</sub>. Similarly, immunization by scarification on the skin fully protected against death, but not from mild disease. This data demonstrates that the Washington strain spike, when expressed from a highly attenuated, replication-competent poxvirus—administered without parenteral injection—can fully protect against the heavily mutated mouse-adapted SARS2-N501Y<sub>MA30</sub>.https://www.mdpi.com/2076-393X/10/8/1172vaccineSARS-CoV-2replication-competent |
| spellingShingle | Karen V. Kibler Mateusz Szczerba Douglas Lake Alexa J. Roeder Masmudur Rahman Brenda G. Hogue Lok-Yin Roy Wong Stanley Perlman Yize Li Bertram L. Jacobs Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501Y<sub>MA30</sub> Strain of SARS-CoV-2 Vaccines vaccine SARS-CoV-2 replication-competent |
| title | Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501Y<sub>MA30</sub> Strain of SARS-CoV-2 |
| title_full | Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501Y<sub>MA30</sub> Strain of SARS-CoV-2 |
| title_fullStr | Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501Y<sub>MA30</sub> Strain of SARS-CoV-2 |
| title_full_unstemmed | Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501Y<sub>MA30</sub> Strain of SARS-CoV-2 |
| title_short | Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501Y<sub>MA30</sub> Strain of SARS-CoV-2 |
| title_sort | intranasal immunization with a vaccinia virus vaccine vector expressing pre fusion stabilized sars cov 2 spike fully protected mice against lethal challenge with the heavily mutated mouse adapted sars2 n501y sub ma30 sub strain of sars cov 2 |
| topic | vaccine SARS-CoV-2 replication-competent |
| url | https://www.mdpi.com/2076-393X/10/8/1172 |
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